Abstract
In the present study, we characterized hydrogen peroxide (H2O2)-induced cell apoptosis and related cell signaling pathways in cultured embryonic neural stem/progenitor cells (NS/PCs). Our data indicated that H2O2 induced acute cell apoptosis in NS/PC in concentration- and time-dependent manners and selectively, it transiently increased PI3K-Akt and Mek-Erk1/2 in a dose-dependent manner. Inhibition of PI3K-Akt with wortmannin, a PI3-K inhibitor, was found to significantly increase H2O2-induced acute apoptosis and dramatically decrease basal pGSK3beta levels. The level of pGSK3beta remained unchanged with H2O2 exposure. We conclude that the transient activation of PI3K-Akt signaling delays the H2O2-induced acute apoptosis in cultured NS/PCs in part through maintaining the basal pGSK3beta level and activating other downstream effectors.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Androstadienes / pharmacology
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Animals
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Apoptosis*
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Blotting, Western
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Brain / embryology
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Cell Death
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DNA Fragmentation
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Densitometry
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Fluoresceins / metabolism
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Hydrogen Peroxide / pharmacology*
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Immunohistochemistry
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In Situ Nick-End Labeling
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Neurons / cytology
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Neurons / metabolism
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Neurons / pathology*
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Oxidative Stress
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Phosphorylation
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Propidium / pharmacology
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Signal Transduction
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Stem Cells / cytology
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Stem Cells / pathology*
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Time Factors
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Wortmannin
Substances
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Androstadienes
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Enzyme Inhibitors
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Fluoresceins
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Proto-Oncogene Proteins
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Propidium
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Hydrogen Peroxide
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Akt1 protein, rat
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Glycogen Synthase Kinase 3 beta
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Glycogen Synthase Kinase 3
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fluorexon
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Wortmannin